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The pharmacokinetics and pharmacodynamics of intravenous magnesium sulfate in horses

Schumacher, Stephen A
http://rave.ohiolink.edu/etdc/view?acc_num=osu1562104626668678

Abstract Details

2019, Doctor of Philosophy, Ohio State University, Comparative and Veterinary Medicine.
Intravenous administration of magnesium sulfate (MgSO4) is used to calm horses in equestrian competitions, which is contrary to the rules, and there are no current means to regulate its administration. Initial pilot data from magnesium sulfate (MgSO4) administrations identified increases in plasma ionized magnesium (Mg2+) concentrations and changes in the plasma ionized calcium (Ca2+) to Mg2+ concentration ratio. Three experiments were designed to evaluate these changes and to investigate the pharmacokinetics and pharmacodynamics of MgSO4 administration with a goal to identify regulatory methods for its control in horses. The first study investigated the effect the processing, handling, and storage procedures, of the United States Equestrian Federations Equine Drugs and Medications Program, have on Mg2+ and related electrolytes in a sample of 50 normal horses. It was concluded that these procedures could be used to establish regulatory thresholds through the use of electrolyte biomarkers for the administration of MgSO4. The second study detailed the pharmacokinetics of MgSO4 administration and included an investigation of the potential mechanism by which MgSO4 exerts its calming effect. This study examined pharmacodynamic related changes in cardiovascular and fractional excretion variables, as well as, changes in the endocrine profile and electrolyte levels in cerebrospinal fluid as a result of a 60 mg/kg intravenous administration of MgSO4. This study did not include a control group as it was not possible to maintain restraint on these intensively instrumented horses for 6 hours without the aid of MgSO4. It was concluded that the intravenous administration of MgSO4 decreased mean arterial blood pressures, increased left ventricular function, increased the fractional excretion of electrolytes, altered the endocrine profile for calcitonin and parathyroid hormone, but did not result in changes to concentrations of Mg2+ in the cerebrospinal fluid. Additionally, this work confirmed the changes in plasma Mg2+ concentrations and the Ca2+ to Mg2+ ratio as seen in the pilot data. In the third study, which was tightly controlled, a novel radiotelemetric approach was used to further elucidate the pharmacodynamics of intravenous MgSO4 administration without the need to for restraint of the horses. This technology was used to document changes in blood pressure, electrocardiograms, and locomotion in response to horses administered 60 mg/kg of MgSO4. We were able to demonstrate a decrease in blood pressure, changes in electrocardiogram conduction intervals, and a decrease in locomotion, all of which could be related to the calming effects of intravenous MgSO4 in horses. Conclusions drawn from these three studies include the identification of regulatory biomarkers capable of determining intravenous MgSO4, a decrease in blood pressure as the likely mechanism for calming, a decrease in activity as a result of administration, and the identification of potential endocrine biomarkers for regulatory control in the form of calcitonin and parathyroid hormone. Additional work is necessary and ongoing to further evaluate and develop thresholds for calcitonin and parathyroid hormone.
Alicia Bertone, DVM, PhD (Advisor)
Ramiro Toribio, DVM, MA, PhD (Committee Member)
Jeffrey Lakritz, DVM, PhD (Committee Member)
Phillip Lerche, BVSc, PhD (Committee Member)
Teresa Burns, DVM, PhD (Committee Member)
119 p.
Pharmacology; Veterinary Services

Recommended Citations

Citations

  • Schumacher, S. A. (2019). The pharmacokinetics and pharmacodynamics of intravenous magnesium sulfate in horses [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1562104626668678

    APA Style (7th edition)

  • Schumacher, Stephen. The pharmacokinetics and pharmacodynamics of intravenous magnesium sulfate in horses . 2019. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1562104626668678.

    MLA Style (8th edition)

  • Schumacher, Stephen. "The pharmacokinetics and pharmacodynamics of intravenous magnesium sulfate in horses ." Doctoral dissertation, Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1562104626668678

    Chicago Manual of Style (17th edition)

osu1562104626668678
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This open access ETD is published by The Ohio State University and OhioLINK.